Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges

PMC6446912Chronic infection with hepatitis C virus is a major cause of liver disease and hepatocellular carcinoma worldwide. After the discovery of hepatitis C virus 3 decades ago, the identification of the structure of the viral proteins, combined with high-throughput replicon models, enabled the discovery and development of direct-acting antivirals. These agents have revolutionized patient care, with cure rates of more than 90%. We review the status of direct-acting antiviral therapies for hepatitis C virus infection and discuss remaining challenges. We highlight licensed compounds, discuss the potential to shorten therapy even further, and review different options for treatment failure and resistance. We also provide an overview of clinical experience with generic agents and evidence for their efficacy. Finally, we discuss the need for new drugs and outline promising targets for future therapies

Complete Solving for Explicit Evaluation of Gauss Sums in the Index 2 Case

Let $p$ be a prime number, $q=p^f$ for some positive integer $f$, $N$ be a positive integer such that $\gcd(N,p)=1$, and let \k be a primitive multiplicative character of order $N$ over finite field \fq. This paper studies the problem of explicit evaluation of Gauss sums in "\textsl{index 2 case}" (i.e. f=\f{\p(N)}{2}=[\zn:\pp], where \p(\cd) is Euler function). Firstly, the classification of the Gauss sums in index 2 case is presented. Then, the explicit evaluation of Gauss sums G(\k^\la) (1\laN-1) in index 2 case with order $N$ being general even integer (i.e. N=2^{r}\cd N_0 where $r,N_0$ are positive integers and $N_03$ is odd.) is obtained. Thus, the problem of explicit evaluation of Gauss sums in index 2 case is completely solved

Hidden Markov models based on symbolic dynamics for statistical modeling of cardiovascular control in hypertensive pregnancy disorders

Copyright © 2006 IEEEDiscrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.V. Baier, M. Baumert, P. Caminal, M. Vallverdú, R. Faber, and A. Vos

Coherent control using adaptive learning algorithms

We have constructed an automated learning apparatus to control quantum systems. By directing intense shaped ultrafast laser pulses into a variety of samples and using a measurement of the system as a feedback signal, we are able to reshape the laser pulses to direct the system into a desired state. The feedback signal is the input to an adaptive learning algorithm. This algorithm programs a computer-controlled, acousto-optic modulator pulse shaper. The learning algorithm generates new shaped laser pulses based on the success of previous pulses in achieving a predetermined goal.Comment: 19 pages (including 14 figures), REVTeX 3.1, updated conten

A note on the Griesmer bound

Griesmer's lower bound for the word length n of a linear code of dimension k and minimum distance d is shown to be sharp for fixed k, when d is sufficiently large. For k ≤ 6 and all d the minimum word length is determined

Hepatitis B virus receptors and molecular drug targets

Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. Virus-induced diseases include cirrhosis, liver failure and hepatocellular carcinoma. Current therapeutic strategies may at best control infection without reaching cure. Complementary antiviral strategies aimed at viral cure are therefore urgently needed. HBV entry is the first step of the infection cycle, which leads to the formation of cccDNA and the establishment of chronic infection. Viral entry may thus represent an attractive target for antiviral therapy. This review summarizes the molecular virology and cell biology of HBV entry, including the discovery and development of new HBV entry inhibitors, and discusses their potential in future treatment of HBV infection